Lanthanum chloride suppresses hydrogen peroxide-enhanced calcification in rat calcifying vascular cells.
Lanthanum chloride (LaCl(3)) has been shown to retard the progression of established atherosclerotic lesions in animal models, and used as a calcium channel blocker in various cellular experiments. In this study, we assessed the role of lanthanum chloride (LaCl(3)) in H(2)O(2)-enhanced calcification in rat calcifying vascular cells (CVCs) and examined the involvement of MAPK signaling pathways. H(2)O(2) induced growth inhibition of CVCs, as well as increases in intracellular levels of calcium and reactive oxygen species, ALP activity, apoptosis and calcium deposition. These effects of H(2)O(2) were suppressed by pretreatment of the cells with 1 muM of LaCl(3) for 2 h. In addition, H(2)O(2) activated the phosphorylation of ERK1/2, JNK and p38 MAPK, but only the last two were associated with the ALP activity. Our findings demonstrate that H(2)O(2)-enhanced osteoblastic differentiation and apoptosis are responsible for the increased calcification in rat CVCs, and LaCl(3) can counteract these effects by suppressing the activation of JNK (JNK2, but not JNK1) and p38 MAPK signaling pathway.
Shi
Yu
Y
Department of Chemical Biology, Peking University School of Pharmaceutical Sciences, 38 Xueyuan Road, Beijing, 100191, People's Republic of China.
Gou
Bao-Di
BD
Shi
Yan-Ling
YL
Zhang
Tian-Lan
TL
Wang
Kui
K
D000818:Animals; D001011:Aorta / Q000473:pathology; D017209:Apoptosis; D002118:Calcium / Q000737:chemistry*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000737:chemistry*; D007811:Lanthanum / Q000494:pharmacology*; D020935:MAP Kinase Signaling System; D010006:Osteoblasts / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; D013844:Thiazoles; C028521:lanthanum chloride; D007811:Lanthanum; D006861:Hydrogen Peroxide; D048051:p38 Mitogen-Activated Protein Kinases; C022616:thiazolyl blue; D002118:Calcium